Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced new data from two pivotal Phase III efficacy trials for suvorexant, the investigational medicine Merck is developing for the treatment of insomnia. In the studies, suvorexant significantly reduced the time it took patients to fall asleep and increased the time that patients stayed asleep as early as the first night and at the three-month time point compared to placebo. The investigational medicine met statistical significance for all primary endpoints except for one measurement at Month 3 in one of the trials. These late-breaking data were presented here today at SLEEP 2012, the 26th Annual Meeting of the Associated Professional Sleep Societies.

"This investigational drug targets insomnia in a way that is different from other medicines," said Andrew D. Krystal, M.D., professor of Psychiatry and Behavioral Sciences, Duke University Medical Center. "The potential for a new and different option would be welcome by patients with insomnia who cannot sleep through the night."

Further efficacy and safety results from the Phase III clinical program for suvorexant were presented at the SLEEP meeting. In these two pivotal Phase III efficacy trials, the most common adverse events (AEs) reported at an incidence of greater than or equal to five percent and more often than placebo were sleepiness and headache. Other data presented included results that demonstrated the effects of suvorexant after daily dosing for at least a year (abstract 0641, oral session O22). This is one of the longest continuously dosed, placebo-controlled trials of a sleep medication ever conducted. Results from a driving study in elderly patients also were presented (abstract 0670, poster 192). Merck plans to present additional results from its two pivotal Phase III efficacy trials later this year.

Merck researchers developed suvorexant to target and block orexins, chemical messengers that originate from the hypothalamus (an important sleep center in the brain) that help to keep you awake. By blocking the actions of orexins, suvorexant helps to facilitate sleep. Merck plans to file a New Drug Application (NDA) for suvorexant with the U.S. Food and Drug Administration (FDA) in 2012, making it one of the company’s six major filings planned for 2012 and 2013. If approved, suvorexant would be the first medicine approved in a new class of medicines, called orexin receptor antagonists, for use in patients with difficulty falling or staying asleep. Merck anticipates that suvorexant will be evaluated by the Controlled Substance Staff of the FDA.

“We specifically focused our research efforts on insomnia because it is an area of significant unmet medical need,” said Darryle D. Schoepp, Ph.D., senior vice president and head of Neuroscience and Ophthalmology franchise, Merck Research Laboratories. “Suvorexant approaches insomnia differently than other medicines because it helps patients to sleep by targeting and blocking orexins, which play a role in keeping people awake. We’re excited about the Phase III results and the potential of suvorexant to become the first in a new class of medicines to help patients with insomnia.”

Studies Measured Effect of Suvorexant on Sleep Onset and Maintenance

Merck’s two pivotal Phase III efficacy studies were multicenter, randomized, double-blind, placebo-controlled trials of suvorexant in patients with primary insomnia (1,021 and 1,009 treated patients in Trial 1 and Trial 2, respectively). Primary insomnia is defined as difficulty falling or staying asleep or poor sleep quality that is the main condition experienced (not caused by another medical problem). A high and a low dose of suvorexant were studied in each trial. The high dose evaluated suvorexant 40 mg in patients 18-64 years and suvorexant 30 mg in patients 65 years and older, and the low dose assessed suvorexant 20 mg in patients 18-64 years and suvorexant 15 mg in patients 65 years and older. Patients were randomized to receive one of the suvorexant doses or placebo over a three-month period. The results reported below are for the combined primary endpoint dose of 40 mg and 30 mg (383 patients in Trial 1 and 387 patients in Trial 2 were treated with the high dose compared to 384 and 383 on placebo, respectively).

The endpoints for the studies included mean change from baseline for suvorexant compared to placebo in both subjective (patient-reported) and objective (polysomnographic, sleep lab-based, assessed in a subset of patients) measures of sleep onset and sleep maintenance. The subjective measures included time it took to fall asleep and total sleep time. Subjective endpoints were measured after one and three months (primary endpoints) and over the first week (a secondary endpoint) of taking suvorexant or placebo. The objective measures included time it took to fall into continuous sleep and time spent awake during the night. Objective endpoints were measured after one and three months (primary endpoints) and after the first night (a secondary endpoint) of taking suvorexant or placebo.

Results for Objective and Subjective Measures

In both trials, on all primary subjective measures, patients who took suvorexant fell asleep significantly faster and stayed asleep longer compared to patients taking placebo at one month and three months (p<0.003). On the objective measures, suvorexant also significantly reduced the time it took patients to fall into continuous sleep and decreased the time patients spent awake during the night at one month and three months (primary endpoints), and as early as night one (a secondary endpoint) (p<0.001), except for Month 3 in Trial 2, at which point the difference in time to fall into continuous sleep did not reach statistical significance.

Specifically, at three months in Trial 1, patients reported suvorexant reduced the time it took them to fall asleep by 25.7 minutes (vs. 17.3 minutes with placebo) and helped them to sleep 60.3 minutes longer (vs. 40.6 minutes with placebo) compared to before they started taking suvorexant. For the objective measures, patients taking suvorexant entered into continuous sleep 36.0 minutes faster (vs. 26.6 minutes with placebo) and spent less time awake during the night by 47.9 minutes (vs. 25.0 minutes with placebo) compared to before they started taking suvorexant. (All of these differences between suvorexant and placebo were statistically significant.)

At three months in Trial 2, patients reported suvorexant reduced the time it took them to fall asleep by 33.7 minutes (vs. 20.5 minutes with placebo) and helped them to sleep 62.8 minutes longer (vs. 37.7 minutes with placebo) compared to before they started taking suvorexant. For the objective measures at three months, suvorexant did not achieve statistical significance on the measure of patients falling into continuous sleep faster than with placebo (-32.2 minutes vs. -28.6 minutes, p=0.265). The objective data showed that patients taking suvorexant spent less time awake during the night by 54.2 minutes (vs. 24.8 minutes with placebo) compared to before they started taking suvorexant. (All of these differences were statistically significant except for the one noted above.)

In these studies, secondary objective measurements included the time it took patients to fall into continuous sleep and the time patients spent awake during the night on night one. In Trial 1, patients taking suvorexant entered into continuous sleep 30.6 minutes faster (vs. 20.3 minutes with placebo) and spent less time awake during the night by 58.0 minutes (vs. 19.6 minutes with placebo) compared to before they started taking suvorexant. In Trial 2, patients taking suvorexant entered into continuous sleep 34.7 minutes faster (vs. 13.0 minutes with placebo) and spent less time awake during the night by 63.3 minutes (vs. 21.3 minutes with placebo) compared to before they started taking suvorexant.

Safety Results

Over three months, the overall incidence of AEs reported as related to the medicine in patients who took the high dose of suvorexant compared to placebo was 25.1 percent versus 13.8 percent in Trial 1, and 22.2 percent versus 16.4 percent in Trial 2. The overall incidence of discontinuations due to an AE in patients who received the high dose of suvorexant compared to placebo was 4.7 percent versus 6.0 percent in Trial 1, and 4.7 percent versus 4.4 percent in Trial 2. No serious drug-related AEs were observed in either trial with the high dose of suvorexant. The most common AEs that occurred at an incidence of greater than or equal to five percent and more often than placebo in patients who received the high dose of suvorexant were sleepiness (10.7 percent vs. 3.4 percent with placebo in Trial 1; 10.3 percent vs. 3.1 percent with placebo in Trial 2) and headache (6.8 percent vs. 6.0 percent with placebo in Trial 1; 7.5 percent vs. 5.7 percent with placebo in Trial 2).

In the overall study population, there were no statistically significant next day objective residual effects compared to placebo as measured by the Digit Symbol Substitution Test (an assessment of memory, attention, visual scanning and perceptual and motor speed). Additionally, patients reported incidence of next day sleepiness at three months were 10.7 percent for high dose of suvorexant versus 3.4 percent for placebo in Trial 1, and 10.3 percent versus 3.1 percent in Trial 2. Cataplexy, an abrupt and temporary loss of muscle control, was not reported in either study. Patients with narcolepsy or cataplexy were excluded from these trials.

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